This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To understand the "correlates of control" in macaque elite controllers (ECs). The "correlates of protection," i.e., the immune responses which will protect vaccinated individuals against HIV infection, are unknown. Because of this, there is intense interest in studying "elite controllers" (ECs), rare individuals who spontaneously control HIV replication. Over the past few years we have assembled a cohort of elite controller macaques that resemble human ECs in several important respects. This project is aimed at understanding the "correlates of control" in these macaque ECs. Previously we showed that elite control in our macaque cohort was associated with expression of particular MHC class I (MHC-I) alleles, Mamu-B*17 and Mamu-B*08. Strikingly, all macaque elite controllers in our cohort express at least one of these alleles. These proteins present peptide "epitopes" derived from SIV proteins to CD8+ T cells, "flagging" infected cells for destruction. Since Mamu-B*17 and B*08 play a role in the cellular immune response, we therefore hypothesized that the specific CD8+ T cell responses made by animals expressing these proteins made it possible for them to become ECs. This project has therefore probed the contribution of CD8+ T cell responses, particularly those "restricted" by Mamu-B*17 and B*08, to immune containment of SIV in macaque ECs. Not all Mamu-B*17- or B*08-positive macaques become ECs when they are infected with SIV. To understand what distinguishes successful and unsuccessful responses, we therefore comprehensively compared the cellular immune responses to SIV in EC and progressor macaques that all expressed Mamu-B*17. Strikingly, we found no apparent differences in either the strength of immune responses or number of viral epitopes recognized in ECs and progressors (1). Current studies are aimed at determining whether particular CD8+ T cell responses are correlated with the ability of Mamu-B*17-positive ECs to resist rechallenge with divergent viruses. This research used WNPRC Animal Services, Genetics Services, and Immunology &Virology Services.